Centro de Investigaciones del Hombre en el Desierto (CODECITE-CIHDE), Arica, Chile.
Departamento de Biología, Facultad de Ciencias, Universidad de Tarapacá, Arica, Chile.
Int J Oncol. 2014 Apr;44(4):1357-64. doi: 10.3892/ijo.2014.2302. Epub 2014 Feb 14.
Breast cancer is the second cause of cancer‑related deaths in woman and the incidence of the disease has increased worldwide, in part due to improvements in early detection. Several drugs with anticancer effects have been extracted from plants in the last 20 years, many of which are particularly effective against breast cancer cells. In particular, we have become interested in the ethanolic extract from Senecio graveolens (synonym of S. nutans), a plant commonly called Chachacoma, in an effort to isolate compounds that could demonstrate cytotoxic effects on breast cancer cells. Senecio (Asteraceae) is the largest gender in Chile comprising approximatly 200 species. These herbs inhabit areas over 3,500 meters above the sea level in the Andes Mountains. S. graveolens is commonly used by local communities for its medicinal properties, particularly its capacity to ameliorate high-altitude-associated sickness. The cytotoxic effect of the alcoholic extract from S. graveolens, as well as its most abundant compound 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone, were tested in the breast cancer cell lines ZR-75-1, MCF-7 and MDA-MB‑231, and non-tumorigenic MCF-10F cells. We show that the phytochemical extract was able to induce cytotoxicity in cancer cells but not in MCF-10F. Importantly, this effect was enhanced under hypoxic conditions. However, 4-hydroxy-3-(3-methyl-2-butenyl)acetophenone, the main compound, did not by itself show an effective anticarcinogenic activity in comparison to the whole extract. Interestingly, the cytotoxic effect of the phytochemical extract was dependent on the basal MnSOD protein expression. Thus, cytotoxicity was increased when MnSOD levels were low, but resistance was evident when protein levels were high. Additionally, the crude extract seems to trigger cell death by a variety of processes, including autophagy, apoptosis and necrosis, in MCF-7 cells. In summary, S. graveolens extract possess anticancer activity displaying a specific cytotoxic effect on cancer cells, thus serving as a potential source of phytochemical compounds for cancer treatment.
乳腺癌是女性癌症相关死亡的第二大原因，全球范围内该病的发病率有所上升，部分原因是早期检测水平的提高。在过去的 20 年中，从植物中提取了几种具有抗癌作用的药物，其中许多对乳腺癌细胞特别有效。特别是，我们对 Senecio graveolens（同义词为 S. nutans）的乙醇提取物产生了兴趣，这种植物通常被称为 Chachacoma，目的是分离出可能对乳腺癌细胞具有细胞毒性作用的化合物。Senecio（菊科）是智利最大的性别，约有 200 种。这些草本植物栖息在安第斯山脉海拔 3500 米以上的地区。S. graveolens 常被当地社区用于其药用特性，特别是缓解高原病的能力。我们测试了 S. graveolens 的乙醇提取物及其最丰富的化合物 4-羟基-3-(3-甲基-2-丁烯基）苯乙酮对乳腺癌细胞系 ZR-75-1、MCF-7 和 MDA-MB-231 以及非致瘤 MCF-10F 细胞的细胞毒性作用。我们表明，植物化学提取物能够诱导癌细胞的细胞毒性，但不能诱导 MCF-10F 细胞的细胞毒性。重要的是，这种作用在缺氧条件下增强。然而，与整个提取物相比，主要化合物 4-羟基-3-(3-甲基-2-丁烯基）苯乙酮本身并没有表现出有效的抗癌活性。有趣的是，植物化学提取物的细胞毒性作用取决于基础 MnSOD 蛋白表达。因此，当 MnSOD 水平较低时，细胞毒性增加，但当蛋白水平较高时，耐药性明显。此外，在 MCF-7 细胞中，粗提取物似乎通过多种过程触发细胞死亡，包括自噬、细胞凋亡和坏死。总之，S. graveolens 提取物具有抗癌活性，对癌细胞表现出特异性细胞毒性作用，因此可能成为癌症治疗的植物化学化合物的潜在来源。
